CN103720652A - Abamectin-drug-containing injection prepared from poloxamer and oily medium - Google Patents
Abamectin-drug-containing injection prepared from poloxamer and oily medium Download PDFInfo
- Publication number
- CN103720652A CN103720652A CN201410005519.9A CN201410005519A CN103720652A CN 103720652 A CN103720652 A CN 103720652A CN 201410005519 A CN201410005519 A CN 201410005519A CN 103720652 A CN103720652 A CN 103720652A
- Authority
- CN
- China
- Prior art keywords
- injection
- medicine
- preparation
- liter
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to an abamectin-drug-containing injection prepared from poloxamer and oily medium, which is prepared by the following steps: combining abamectin drug with poloxamer 407 to obtain drug-carrying granules; and dispersing the drug-carrying granules in the oily medium, and grinding to obtain the oily long-acting injection containing abamectin drug/poloxamer 407 drug-carrying granules. Hydroxypropyl methylcellulose or highly-substituted hydroxypropyl cellulose can also be added into the drug-carrying granules to obviously enhance the slow-release action of the preparation. The injection has the advantages of simple preparation technique, uniform drug release, favorable biocompatibility, no irreversible injury on tissues in the injection site, and degradable and removable slow-release carrier.
Description
Technical field
The invention belongs to veterinary drug preparation technology of preparing, be specifically related to poloxamer188 and oil medium be carrier, preparation is containing the long-acting veterinary injection of Avermectins medicine.
Background technology
Poloxamer is polyoxyethylene polyoxypropylene ether analog copolymer, this base polymer has plurality of specifications, wherein the aqueous solution of poloxamer188 (hereinafter to be referred as P407) has " characteristic being transformed to gel by colloidal sol with temperature rising ", generally at 30 ℃, there is above gelling in certain density P407 aqueous solution, characteristic accordingly, P407 is used to the preparation of slow releasing injection, and said preparation is referred to as in-situ gelling preparation.After being injected in vivo containing the in-situ gelling injection of P407, under the effect of body temperature, generally, about 1 minute, by colloidal sol, change gel (semisolid) into, medicine is wrapped in gel, thereby has slowed down rate of releasing drug, and duration of efficacy is extended.The disclosed in-situ gelling injection containing P407 of document and patent, the solvent of its preparation is water, in preparation, the concentration of P407 will reach and more than 20% just have good slow releasing function; In preparation, add the blocker such as a certain amount of methylcellulose, sodium carboxymethyl cellulose, Hydroxypropylcelliloxe (H-HPC) or hydroxypropyl emthylcellulose (HPMC), can strengthen slow releasing function, but can cause preparation viscosity to raise, make injection more difficult.
P407 is also the good non-ionic surface active agent of a kind of water solublity, is to be more used to prepare Emulsion, ointment, aqueous suppository, drop pill etc.; P407 is also used as the dispersible carrier of insoluble medicine (medicine that water solublity is very poor), and for the preparation of solid solution, mostly the published solid solution of preparing with P407, be the preparation for oral preparations.
The present invention is different from published technology, the present invention is by the medicine carrying microgranule (as agglomerate) of medicine and P407 (or with P407 and cellulose ethers) composition solid solution or other form, and (isopropyl myristate, hereinafter to be referred as IPM with oil medium; Injection vegetable oil) place of water prepares the oily injection containing P407 medicine carrying microgranule.This preparation injects under animal skins or intramuscular, medicine carrying microgranule is after " breakthrough " oil phase contact body fluid (water), by means of P407 " water suction (body fluid) " or water absorption and swelling (when HPMC or H-HPC exist), " adhesive aggregation " together, in injection site, form high concentration and full-bodied and there is the semi-solid agglomerate of " bioadhesive " (when HPMC or H-HPC exist), medicine is wrapped in agglomerate, thereby has effectively extended drug release time.And due to the peptizaiton of P407, make insoluble medicine release more complete, thereby improved the bioavailability of hydrophobic drug, reduced injection site drug residue.
The medicine the present invention relates to is Avermectins medicine, comprises ivermectin Ivermectin, avilamycin Avermectin, Eprinomectin Eprinomectin, doractin Doramectin, milbemycin oxime Milbemycin Oxime, moxidectin Moxidectin.This experiment demonstration, Avermectins medicine can be combined into medicine carrying microgranule with P407 or with P407/HPMC (or H-HPC), and is scattered in oil medium, prepares outstanding slow releasing injection.Above Avermectins medicine is mainly used in preventing and treating nematicide and the epizootic disease of the animals such as pig, cattle, sheep at veterinary clinic, their " character, pharmacology and purposes " etc. are < < veterinary drug handbook > > (Zhu Mozhong chief editor, Chemical Industry Press, July in 2002 the 1st edition, 167-174 page) and open source literature in all on the books and describe.Containing the commercially available injection of Avermectins medicine, majority be with organic solvent (as 1,2-PD, N-Methyl pyrrolidone, formal glycerine etc.) or the grease compounds of synthetic be solution type preparation prepared by solvent; The disclosed injection containing Avermectins medicine of document or patent has solution type preparation, suspension type preparation, Emulsion, have containing microsphere or microcapsule or containing the long-acting injection of different slow-released carriers (as polyvinylpyrrolidone, polylactic acid, PLGA, Sucrose acetoisobutyrate, castor oil hydrogenated, Semen Ricini wet goods).But have no report containing Avermectins medicine/P407 medicine carrying microgranule or containing the oily long-acting injection of Avermectins medicine/P407/HPMC (or H-HPC) medicine carrying microgranule.
Summary of the invention
In this preparation, therefore medicine and P407 or medicine and P407 and HPMC (or H-HPC) form medicine carrying microgranule, and are suspended in oil medium, with medicine carrying microgranule state, this preparation is different from the in-situ gelling preparation that contains P407 take water as medium, is also different from traditional oily injection.Preparation composition of the present invention and preparation method are as follows:
Preparation composition: this preparation is mainly comprised of Avermectins medicine, P407 and oil medium.In every liter of injection, containing Avermectins medicine 25-100g, P40725-100g, oil medium, add to 1 liter.
Described Avermectins medicine comprises: ivermectin Ivermectin, avilamycin Avermectin, Eprinomectin Eprinomectin, doractin Doramectin, milbemycin oxime Milbemycin Oxime, moxidectin Moxidectin.These Avermectins medicines are commercialization all, in < < Chinese veterinary pharmacopoeia > > and veterinary drug handbook and pertinent literature, all can find.
Described oil medium is IPM or injection soybean oil or Semen Maydis oil or Oleum Camelliae.
In above-described every liter of injection, also can add 20-70g HPMC or H-HPC, HPMC or H-HPC need be combined into solid solution or form medicine carrying microgranule with P407 together with Avermectins medicine with P407, could be used for the preparation of this preparation.H-HPC has good dissolubility in the low boiling point organic solvents such as methanol, ethanol, Avermectins medicine has equally good dissolubility in these low boiling point organic solvents, this is that H-HPC, P407, Avermectins medicine three can form one, is prepared into the important foundation of medicine carrying microgranule.
H-HPC and HPMC be nontoxic, without pharmacological action, on physiologically active, show extreme inertia.HPMC, H-HPC or P407 are insoluble in the oil mediums such as IPM, therefore, by H-HPC or HPMC and P407 composition microgranule, even be scattered in oil medium with higher concentration, can not make preparation viscosity obviously raise yet, but contain the medicine carrying microgranule of high concentration H-HPC or HPMC at injection part energy water absorption and swelling, form full-bodied agglomerate, full-bodied agglomerate has the effect of stronger retardance (slowing down) drug release, therefore, as requested, in medicine carrying microgranule, add appropriate H-HPC and HPMC and can reach the slow release effect of expection.
Avermectins medicine exists with medicine carrying microgranule state in this preparation, and medicine carrying microgranule is comprised of Avermectins medicine and P407, or forms with P407/H-HPC (or and P407/HPMC).
In the medicine carrying microgranule of Avermectins medicine and P407 composition, its weight ratio is 1: 0.5-1, and the weight/volume percent content of medicine carrying microgranule in preparation is 5-20%, surplus is oil medium.
In the medicine carrying microgranule of Avermectins medicine and P407 and HPMC composition, Avermectins medicine, P407, HPMC three's weight ratio is 1: 0.5-1: 0.3-0.7, the weight/volume percent content of medicine carrying microgranule in preparation is 5.5-20%, preferred weight/volume percent content is 8-16%, and surplus is oil medium.
In the medicine carrying microgranule of Avermectins medicine/P407/H-HPC composition, Avermectins medicine, P407, H-HPC three's weight ratio is 1: 0.5-1: 0.3-0.7, the weight/volume percent content of medicine carrying microgranule in preparation is 5.5-20%, preferred weight/volume percent content is 8-16%, and surplus is oil medium.
Preparation method: be summed up and mainly contain following two kinds.
(1) under heating condition, Avermectins medicine and P407 or Avermectins medicine and P407 and HPMC or Avermectins medicine and P407 and H-HPC mono-are reinstated to low boiling point solvent to be dissolved, then distilling under reduced pressure, remove low boiling point solvent, obtain Avermectins medicine/P407 solid solution or Avermectins medicine/P407/HPMC solid solution or Avermectins medicine/P407/H-HPC solid solution; The solid solution of preparation was pulverized to 40 mesh sieves, obtained medicine carrying microgranule; Medicine carrying microgranule is scattered in part oil medium, with colloid mill, be ground to particle diameter and be less than 100 μ m, with sand mill, be ground to particle diameter again and be less than 20 μ m, add remaining media to final volume, with high-shear homogenizing machine, under 5000-10000rpm, further homogenize and obtain this preparation.
(2) Avermectins medicine and P407 or Avermectins medicine and solid solution (P407/HPMC or P407/H-HPC) are scattered in part oil medium, with colloid mill and sand mill, be ground to particle diameter and be less than 20 μ m, add remaining media, homogenize and obtain this preparation with high-shear homogenizing machine.
P407/H-HPC or P407/HPMC solid solution preparation: under heating condition, HPMC or H-HPC and P407 be dissolved in to methanol or be dissolved in 80% alcoholic solution, mixing, under agitation removal of solvent under reduced pressure and get final product.
This preparation preparation process need be carried out under aseptic condition, and during grinding, temperature of charge can not exceed 40 ℃, and in preparation, the particle diameter of solid particle should be less than 20 μ m, more suitable to be less than 10 μ m.
This preparation characteristic is summarized as follows:
This medicament drug release process is different from the in-situ gelling preparation take water as medium, is also different from traditional oil preparation, and main difference part is to exist medicine carrying microgranule " breakthrough " oil phase to contact with body fluid and water absorption and swelling formation high viscosity agglomerate process.
By appropriate H-HPC or HPMC and P407 composition solid solution pellet, be scattered in oil phase, solved and with H-HPC (or HPMC) packaging medicine, be difficult to grind to form fine particle and (be less than 20 μ technical barrier m) merely, retain H-HPC and HPMC has water absorption and swelling simultaneously, formed the characteristic of high viscosity agglomerate.Pastille " agglomerate " adheres in injection site tissue, is conducive to medicine and better absorbs, and guaranteed slow release effect to a certain degree, and it is high that this is that this agent has bioavailability, has again the basis of long-acting.
Avermectins medicine is water-soluble hardly, by Avermectins medicine and the application of P407 composition solid solution, can reduce injection site drug residue.
With the preparation of oil medium place of water, contain the slow releasing injection of P407, can reduce the consumption of P407, P407 consumption is when 5-10%, and preparation just has good slow releasing function.Take water as solvent, preparation is containing the in-situ gelling injection of P407, and the consumption of P407 will reach 20～45%, and preparation just can demonstrate good slow releasing function.Current domestic P407 price more expensive (medical grade is at 160～200 yuan/kg), therefore, P407 consumption in preparation is more, and preparation cost is higher, is unfavorable for applying in veterinary applications.
The specific embodiment
Embodiment 1, preparation 6% ivermectin injection
Preparation composition: ivermectin 60g, P40750g, H-HMC45g, IPM add to 1 liter.
Preparation method: (1) by P407 in 60-70 ℃ of thawing, after adding H-HMC to mix, add about 100ml methanol, after H-HMC dissolves, add ivermectin, fully mix, after ivermectin dissolves, distilling under reduced pressure, Ex-all methanol, cooling, after solidifying, pulverize, cross 40 mesh sieves, must be containing the medicine carrying microgranule of ivermectin.(2) medicine carrying microgranule is scattered in part IPM, crossing colloid mill is ground to particle diameter and is less than 50 μ m, further with sand mill, grind, grind to particle diameter and be less than 20 μ m, add remaining media, with high-shear homogenizing machine, under about 5000rpm condition, after repeatedly homogenizing, make the ivermectin injection that particle diameter is less than 20 μ m.
Embodiment 2, preparation 3% avilamycin injection
Preparation composition: avilamycin 30g, P40730g, injection soybean oil adds to 1 liter.
Preparation method: (1) in 60-70 ℃ of thawing, adds P407 avilamycin and is equivalent to the ethanol that avilamycin 4-5 doubly measures, and fully mixes, make it to dissolve, cooling, natural drying after solidifying, pulverize, cross 40 mesh sieves, must be containing the medicine carrying microgranule of avilamycin.(2) medicine carrying microgranule is scattered in part soybean oil, crossing colloid mill is ground to particle diameter and is less than 100 μ m, further with sand mill, grind, grind to particle diameter and be less than 20 μ m, add remaining media, with high-shear homogenizing machine, under about 5000rpm condition, after repeatedly homogenizing, make the avilamycin injection that particle diameter is less than 20 μ m.
Embodiment 3, preparation 9% Eprinomectin injection
Preparation composition: Eprinomectin 90g, P40790g, injection Semen Maydis oil adds to 1 liter.
Preparation method: (1) by P407 in 60-70 ℃ of thawing, add Eprinomectin and be equivalent to the ethanol that Eprinomectin 3-5 doubly measures, reflux and dissolve, ethanol is removed in distilling under reduced pressure, after cooling curing, pulverize, cross 40 mesh sieves, obtain the medicine carrying microgranule of acetamide-containing base avilamycin.(2) medicine carrying microgranule is scattered in part Semen Maydis oil, crossing colloid mill is ground to particle diameter and is less than 100 μ m, further with sand mill, grind, grind to particle diameter and be less than 20 μ m, add remaining media, with high-shear homogenizing machine, under about 5000rpm condition, after repeatedly homogenizing, make the Eprinomectin injection that particle diameter is less than 20 μ m.
Embodiment 4, preparation 5% doractin injection
Preparation composition: add to final volume containing doractin 5g, P407/HPMC (2: 1) solid solution 10g, Oleum Camelliae in every 100ml injection.
Preparation method: doractin and solid solution are scattered in part Oleum Camelliae, are ground to particle diameter with colloid mill and sand mill and are less than 20 μ m, add remaining media, homogenize and obtain this preparation with high-shear homogenizing machine.
Embodiment 5,8% Eprinomectin injection
Preparation comprises Eprinomectin medicine carrying microgranule 160g, and it is comprised of 80g Eprinomectin, 45g poloxamer188,35g HPMC; IPM adds to 1 liter.
Embodiment 6,8% ivermectin injection
Preparation comprises ivermectin medicine carrying microgranule 160g, and it is comprised of 80g ivermectin, 45g poloxamer188,35g HPMC; IPM adds to 1 liter.
Embodiment 7,8% ivermectin injection
Preparation comprises ivermectin medicine carrying microgranule 120g, and it is comprised of 80g ivermectin, 40g poloxamer188; IPM adds to 1 liter.
Embodiment 8, embodiment 1 preparation and the determination of plasma concentration of Comparative formulation in sheep body
Comparative formulation composition: Comparative formulation is containing ivermectin ultramicro powder 6%, P4075%, H-HMC4.5%, and water for injection adds to 100%.
Experimental animal grouping and result of the test: select 10 of healthy sheep, be divided into 2 groups, every group 5, subcutaneous embodiment 1 preparation and the Comparative formulation of injecting respectively of cervical region, dosage is 1.2mg/kg b.w., blood sampling on time, separated plasma, and after the plasma sample of same time is on the same group mixed with acetonitrile extraction, through centrifugal, purify (C
18post), the process such as concentrated, derivatization, make detection sample, adopt ivermectin content in HPLC (fluorescence detector) working sample.Testing result is as shown in the table:
More than in table, numerical value is the meansigma methods of every group of 5 sheep blood plasma drug level.
Claims (7)
1. one kind comprises the veterinary antiparasitic injection of poloxamer188, Avermectins medicine and oil medium.
2. by injection claimed in claim 1, it is characterized in that every liter of injection comprises following composition:
Avermectins medicine 25-100g
Poloxamer188 25-100g
Oil medium adds to 1 liter
Described oil medium is the one in isopropyl myristate or injection soybean oil, Semen Maydis oil, Oleum Camelliae;
Described Avermectins medicine comprises: ivermectin Ivermectin, avilamycin Avermectin, Eprinomectin Eprinomectin, doractin Doramectin, milbemycin oxime Milbemycin Oxime, moxidectin Moxidectin.
3. by the injection described in claim 1 or claim 2 any one, it is characterized in that Avermectins medicine and poloxamer188 composition medicine carrying microgranule, with medicine carrying microgranule state, be present in preparation, the weight/volume percent content of medicine carrying microgranule in preparation is 5-20%.
4. by injection claimed in claim 2, it is characterized in that also can adding hydroxypropyl emthylcellulose or Hydroxypropylcelliloxe 20-60g in every liter of injection, hydroxypropyl emthylcellulose or Hydroxypropylcelliloxe and poloxamer188 combination, with solid solution fine particle state, be present in preparation, or combine with Avermectins medicine and poloxamer188, with medicine carrying microgranule state, be present in preparation.
5. by injection claimed in claim 4, it is characterized in that every liter of injection comprises following composition:
The medicine carrying microgranule 160g being comprised of 80g Eprinomectin, 45g poloxamer188,35g hydroxypropyl emthylcellulose, oil medium adds to 1 liter.
6. by injection claimed in claim 4, it is characterized in that every liter of injection comprises following composition:
The medicine carrying microgranule 160g being comprised of 80g ivermectin, 45g poloxamer188,35g Hydroxypropylcelliloxe, oil medium adds to 1 liter.
7. by injection claimed in claim 3, it is characterized in that every liter of injection comprises following composition:
The medicine carrying microgranule 120g being comprised of 80g ivermectin and 40g poloxamer188, oil medium adds to 1 liter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410005519.9A CN103720652B (en) | 2014-01-07 | 2014-01-07 | Prepare containing Avermectins medicine injection with poloxamer and oil medium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410005519.9A CN103720652B (en) | 2014-01-07 | 2014-01-07 | Prepare containing Avermectins medicine injection with poloxamer and oil medium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103720652A true CN103720652A (en) | 2014-04-16 |
| CN103720652B CN103720652B (en) | 2016-09-28 |
Family
ID=50445119
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410005519.9A Active CN103720652B (en) | 2014-01-07 | 2014-01-07 | Prepare containing Avermectins medicine injection with poloxamer and oil medium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103720652B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104095812A (en) * | 2014-07-30 | 2014-10-15 | 游锡火 | Preparation method for emulsifiable oily injection containing abamectin drugs |
| WO2016138339A1 (en) * | 2015-02-26 | 2016-09-01 | Merial, Inc. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| CN106619685A (en) * | 2016-03-07 | 2017-05-10 | 北京中农华威生物医药研究院 | Oral solid preparation containing ivermectin medicine |
| CN113209012A (en) * | 2021-06-04 | 2021-08-06 | 湖南伟达科技有限公司 | Avermectin transdermal solution and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1193510A (en) * | 1998-04-23 | 1998-09-23 | 王玉万 | Oily injection for preventing animals from parasites |
| CN1354754A (en) * | 1998-11-23 | 2002-06-19 | 株式会社Lgci | Injectable anthelmintic formulation |
| WO2005007241A1 (en) * | 2003-07-12 | 2005-01-27 | Norbrook Laboratories Limited | Parasiticidal composition |
-
2014
- 2014-01-07 CN CN201410005519.9A patent/CN103720652B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1193510A (en) * | 1998-04-23 | 1998-09-23 | 王玉万 | Oily injection for preventing animals from parasites |
| CN1354754A (en) * | 1998-11-23 | 2002-06-19 | 株式会社Lgci | Injectable anthelmintic formulation |
| WO2005007241A1 (en) * | 2003-07-12 | 2005-01-27 | Norbrook Laboratories Limited | Parasiticidal composition |
Non-Patent Citations (1)
| Title |
|---|
| 高存帅等: "注射用泊洛沙姆407温敏型原位凝胶的研究进展", 《中国动物检疫》, vol. 29, no. 5, 31 December 2012 (2012-12-31), pages 72 - 75 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104095812A (en) * | 2014-07-30 | 2014-10-15 | 游锡火 | Preparation method for emulsifiable oily injection containing abamectin drugs |
| CN104095812B (en) * | 2014-07-30 | 2017-09-19 | 北京中农华威制药有限公司 | The preparation method of the emulsifiable oily injection containing Avermectins medicine |
| WO2016138339A1 (en) * | 2015-02-26 | 2016-09-01 | Merial, Inc. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| AU2016222532B2 (en) * | 2015-02-26 | 2018-07-12 | Boehringer Ingelheim Animal Health USA Inc. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| AU2018205137B2 (en) * | 2015-02-26 | 2019-08-08 | Boehringer Ingelheim Animal Health USA Inc. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| US10561641B2 (en) | 2015-02-26 | 2020-02-18 | Boehringer Ingelheim Animal Health USA Inc. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| EA035993B1 (en) * | 2015-02-26 | 2020-09-10 | Мериал, Инк. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| US11484528B2 (en) | 2015-02-26 | 2022-11-01 | Boehringer Ingelheim Animal Health USA Inc. | Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof |
| CN106619685A (en) * | 2016-03-07 | 2017-05-10 | 北京中农华威生物医药研究院 | Oral solid preparation containing ivermectin medicine |
| CN113209012A (en) * | 2021-06-04 | 2021-08-06 | 湖南伟达科技有限公司 | Avermectin transdermal solution and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103720652B (en) | 2016-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103720652A (en) | Abamectin-drug-containing injection prepared from poloxamer and oily medium | |
| CN102824356A (en) | Baicalin nano crystal suspension, nano crystal dry powder and methods for preparing baicalin nano crystal suspension and nano crystal dry powder | |
| CN106063783A (en) | A kind of Progesterone slow-releasing microcapsule preparation and preparation method thereof | |
| CN107811963A (en) | Soluble microneedle device and its application | |
| CN104840430A (en) | Chlorogenic acid (CA) and chitosan microspheres as well as preparation process and application thereof | |
| CN103705452B (en) | Containing the antibacterials injection of poloxamer188 and oil medium | |
| CN101590055B (en) | Water soluble decoquinate and method for preparing same | |
| CN102423300A (en) | Acetyl amino abamectin sustained-release microsphere and preparation method as well as sustained-release microsphere injection | |
| CN105287607A (en) | Compound doxycycline-hydrochloride florfenicol sustained-release microsphere suspension injection for veterinary use | |
| CN103705454B (en) | The oily injection of hydrochloric valnemulin/poloxamer188 | |
| CN103721266A (en) | In-situ gelation injection containing avermectin medicine/hydrogenated castor oil | |
| CN102772363A (en) | Solution with ponazuril and preparation method for solution | |
| CN101310734A (en) | Chinese and western combine compound uterus perfusate for treating cow endometritis | |
| CN101623255B (en) | Artesunate nanoemulsion drug composition and preparation method thereof | |
| CN104138356A (en) | Cinnamaldehyde crosslinked chitosan drug-loading microsphere preparation method | |
| CN103550149A (en) | Technology for preparing long-acting injection containing antiparasitic drugs | |
| CN103721263A (en) | Oil injection containing antibacterial agents/polyethylene glycol drug-loading particles | |
| CN103705455A (en) | Injection containing non-steroidal anti-inflammatory drug and prepared by use of poloxamer and oily medium | |
| CN100544738C (en) | A kind of antineoplastic Chinese medicine preparation | |
| CN103520119B (en) | The preparation method of imidocard dipropionate long-acting veterinary preparation | |
| CN103463088B (en) | A kind of compositions of daily treatment flu and soft capsule | |
| CN103585131A (en) | Preparation method for ivermectin sustained-release gelatin microcapsule | |
| CN103356480A (en) | Oleanolic acid nanometer suspension and preparation method thereof | |
| CN103251556A (en) | Aprepitant nanosuspension and preparation method thereof | |
| CN103705451A (en) | In-situ gelling injection containing praziquantel/hydrogenated castor oil |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170103 Address after: 102206 Beijing City, Miyun Miyun Li Ge Zhuang Cun Zhen Xi Milin No. 128 100 Patentee after: Beijing Zhongnonghuawei feed Technology Co.,Ltd. Address before: 100083 Beijing Qinghua East Road, No. 17,, 41-5-102 Patentee before: Wang Yuwan |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20220927 Address after: 435300 No. 008 Jinshan Road, lishizhen Pharmaceutical Industrial Park, Hexi, Qichun County, Huanggang City, Hubei Province Patentee after: Zhongnong Huawei Biopharmaceutical (Hubei) Co.,Ltd. Address before: No. 128, 100 Milin West, Ligezhuang Village, Miyun Town, Miyun County, Beijing 102206 Patentee before: Beijing Zhongnonghuawei feed Technology Co.,Ltd. |
|
| TR01 | Transfer of patent right |